Citations

e16065 Background: Estrogens, in addition to androgen may contribute to the progression of prostate cancer.The combination of bicalutamide, a non-steroidal anti-androgen, and raloxifene, a selective estrogen receptor modulator, has a synergistic effect on cell death of prostate cancer cell lines such as DU145 and PC3. We investigated the safety of combined treatment of bicalutamide and raloxifene on quality of life in patients affected by hormone-resistant prostate cancer. Methods: Eligibility requirements included metastatic hormone-resistant prostate cancer, Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received the combination of bicalutamide, 50 mg, and raloxifene, 60 mg, daily in 28 day cycles for a maximum of 6 cycles. The primary endpoint was to describe the adverse event profile of combined treatment with bicalutamide and raloxifene. The secondary endpoint was to describe the quality of life of patients receiving the combination. Adverse events were graded by the investigator using the NCI Common Terminology Criteria for Adverse Events version 4.0 and the quality of life was assessed by the patient using aLinear Analog Scale Assessment (scale of 0-100). Serum levels of estradiol and testosterone were monitored during treatment. Results: Eighteen evaluable patients were included in the statistical analysis after an initial run-in safety cohort of six patients. Two patients completed 6 cycles per protocol, the remaining sixteen patients were taken off protocol after disease progression. Patients completed a median of 2 cycles. There were no grade 4 events and grade 3 adverse events consisted of hypertension (5.6%) and back pain (5.6%). Erectile dysfunction (grade 1) was the most common adverse event (77.8%). Patient assessment of quality of life (mental, physical, social, emotional, spiritual) did not reveal any statistically different changes after 2 cycles of treatment. An analysis of testosterone and estradiol levels will be reported. Conclusions: We conclude that combination of bicalutamide and raloxifene is well-tolerated. The combination of androgen and estrogen receptor blockade warrants further study for efficacy in hormone-resistant prostate cancer. Clinical trial information: NCT01050842.

Background: Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Abstract Objective The aim of this study was to evaluate the efficacy and safety of the dopaminergic‐enhancing agent modafinil/armodafinil (MoArm) as adjunctive treatment for bipolar depression. Methods A comprehensive search of major electronic databases was conducted to identify randomized controlled trials (RCTs) of adjunctive MoArm that included patients with bipolar I (BP‐I) or bipolar II (BP‐II) depression. Data for response/remission and all‐cause discontinuation were analyzed. Effect size was summarized by relative risk (RR) using a random effect model. Results Of 58 studies, five RCTs (N = 795 drug, N = 792 placebo) met inclusion criteria. Four armodafinil studies included only BP‐I patients and one modafinil study included both bipolar subtypes with limited heterogeneity ( I 2 = 34%, P = .19; I 2 = 18%, P = .30). Compared to placebo, augmentation with MoArm was associated with significantly greater rates of treatment response (RR, 1.18; 95% CI, 1.01‐1.37; P = .03) and remission (RR, 1.38; 95% CI, 1.10‐1.73; P = .005). All‐cause discontinuation was not different than placebo (RR, 1.08; 95% CI, 0.89‐1.30; P = .45) with no evidence of increased risk of mood switch or suicide attempts with MoArm (RR, 0.99; 95% CI, 0.39‐2.5; P = .98; RR, 1.02; 95% CI, 0.37‐2.85; P = .97). Conclusion This narrower scope meta‐analysis of one drug for one disease suggests that adjunctive MoArm may represent a novel therapeutic intervention. Further studies delineating the subtypes of bipolar depression responsive to these novel dopaminergic‐enhancing agents are encouraged.

Background and Purpose— We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods— We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results— In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99–1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87–1.73) or categorical covariate (likelihood-ratio test 2.59, P =0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60–89, 21.7% for eGFR 45–59, 19.2% for eGFR 30–44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P =0.63). The results were similar for the outcome of death. Conclusions— The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

scikit-image is an image processing library that implements algorithms and utilities for use in research, education and industry applications. It is released under the liberal "Modified BSD" open source license, provides a well-documented API in the Python programming language, and is developed by an active, international team of collaborators. In this paper we highlight the advantages of open source to achieve the goals of the scikit-image library, and we showcase several real-world image processing applications that use scikit-image.

scikit-image is an image processing library that implements algorithms and utilities for use in research, education and industry applications. It is released under the liberal "Modified BSD" open source license, provides a well-documented API in the Python programming language, and is developed by an active, international team of collaborators. In this paper we highlight the advantages of open source to achieve the goals of the scikit-image library, and we showcase several real-world image processing applications that use scikit-image.

Purpose Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic metastases. Methods Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH ‐, AAPM ‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format ( DICOM ‐ CT ‐ PD ). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic ( JAFROC ) figure of merit, which was used for breaking ties. Results 103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data ( CTDI vol = 3.0 ± 1.8 mG y, SSDE = 3.5 ± 1.3 mG y). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing. Conclusion Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.